Biocatalysis in radiochemistry: Enzymatic incorporation of PET radionuclides into molecules of biomedical interest

Abstract

Biocatalysis is emerging as a new approach to radiolabel biologically active molecules with short half-lived positron emitters for their use in positron emission tomography. Despite the golden era of biocatalysis in radiochemistry occurred in the 70s and 80s, advances in enzyme engineering during the last decade have significantly enhanced the toolbox of enzymes available for chemical reactions, which may find application in the context of radiochemistry. In the present review, we intend to give an overview of the biocatalytic approaches that have been reported during the last 4 decades for the synthesis of PET radiotracers using nitrogen-13, carbon-11, and fluorine-18.

Enzymatic synthesis of fluorinated compounds

“…Positron emission tomography (PET) is a non-invasive molecular imaging technique that relies on compounds labeled with positron emitters (da Silva et al 2018 ; Preshlock et al 2016 ). Nowadays, PET has become a valuable tool for detecting pathology in the clinical field.…”

“…Nowadays, PET has become a valuable tool for detecting pathology in the clinical field. Fluorine is a typical positron emitter due to its long half-life (t 1/2 = 110 min), high isotope abundance, large gyromagnetic ratio, sensitivity, and specificity (Clark and O’Hagan 2017 ; da Silva et al 2018 ; Lu et al 2019 ; Troelsen et al 2020 ; Yamamoto et al 2019 ). Since 2-fluorinated glycosides are more stable than glycosides, they can be used as active probes (Sadurni and Gilmour 2018 ).…”

Identification of Two Novel Fluorinases From Amycolatopsis sp. CA-128772 and Methanosaeta sp. PtaU1.Bin055 and a Mutant With Improved Catalytic Efficiency With Native Substrate

“…The first discovered fluorinase was FlA from Streptomyces cattleya ( O'Hagan et al, 2002 ). Due to the ability to work in water under mild conditions, fluorinase has been developed for the preparation of [ 18 F]FDA from SAM and [ 18 F]F − , which can be used in positron emission tomography (PET) for pathologic diagnosis ( da Silva et al, 2018 ). The metabolic pathway of S. cattleya involved with fluorinase has been identified, and a variety of intermediate products have been shown to be the effective pharmaceutical precursors ( O’Hagan and Deng, 2015 ).…”